Tissue and cell development have been studied extensively to determine the mechanisms by which maturation, maintenance, and repair occur in living organisms. Generally, development of a cell or tissue can be considered as a transformation from one state or stage to another relatively permanent state or condition. Development encompasses a wide variety of developmental patterns, all of which are characterized by progressive and systematic transformation of the cells or tissue.
In many instances it is desirable to control or alter the development of cells and tissue in vivo to enhance the quality of life for higher organisms such as man. To this end, science has struggled to provide means by which the natural order of an organism can be maintained or restored in defiance of a debilitating injury, disease or other abnormality. While some prior art therapies have been successful, others have failed to reach their full potential due to unwanted side effects, inferior results, or difficult implementation.
As will be appreciated by those skilled in the art, tissue and organ development involve complex processes of cellular growth, differentiation and interaction mediated by complex biochemical reactions. At the genetic level, development is regulated by genomic expression; at the cellular level, the role of membrane interaction with the complex biochemical milieu of higher organisms is instrumental in developmental processes. Moreover, "remodeling" of tissues or organs is often an essential step in the natural development of higher organisms.
In recent years, multidisciplinary investigations of developmental processes have provided evidence suggesting that electric and magnetic fields play an important role in cell and tissue behavior. In U.S. patent application Ser. No. 923,760, entitled, "Techniques for Enhancing the Permeability of Ions," which has been assigned to the assignee of the present invention and the disclosure of which is incorporated herein by reference, a method and apparatus are disclosed by which transmembrane movement of a preselected ion is magnetically regulated using a timevarying magnetic field. The fluctuating magnetic field is preferably tuned to the cyclotron resonance energy absorption frequency of the preselected ion. This important discovery brought to light the interplay of local geomagnetic fields and frequency dependence in ion transport mechanisms. It has now been discovered that by utilizing and extending the principles of cyclotron resonance tuning, an unexpected and remarkable advance in the control and modification of developmental processes in living tissue can be achieved. In U.S. patent application Ser. No. 172,268 filed Mar. 23, 1988, the disclosure of which is incorporated herein by reference, the inventors of the present invention disclose that cyclotron resonance can be used to control tissue development. In our U.S. patent application entitled "Method and Apparatus For Controlling the Growth of Non-Osseous, Non-Cartilaginous, Solid Connective Tissue," filed Oct. 6, 1988, Ser. No. 254,438, a method of controlling the growth of non-osseous, non-cartilaginous, connective tissue is disclosed which utilizes cyclotron resonance frequencies. In the present application, we disclose a method and apparatus for affecting the growth characteristics of cartilage.
Currently, research efforts in the area of electronic medical devices which affect growth mechanisms in living systems have focused on strain-related bioelectrical phenomena that have been observed in tissue such as bone, tendon and cartilage. During the last few decades, others have noted that electrical potentials are produced in bone in response to mechanical stress. It has been postulated that these electrical potentials mediate the stress-induced structural changes in bone architecture which were observed almost a century ago by J. Wolfe. Hence, although bioelectrical potentials are not well understood, numerous attempts have been made to induce tissue growth with electrical potentials and currents. Much of this research has dealt with the repair of bone non-unions, i.e. bone fractures which have not responded to traditional therapies. Some experimentation has been carried out by others on the effects of electrical stimulation of cartilage, particularly articular cartilage, in an effort to increase the rate of growth and repair of damaged cartilage.
As will be appreciated by those skilled in the art, there are various types of cartilaginous tissues. These are typically classified as hyaline cartilage, fibrocartilage and elastic cartilage. Hyaline cartilage has a matrix comprised of mucopolysaccharide in which chondrocytes are present in lacunae. Collagen fibers are dispersed in the matrix to a limited extent. In fibrocartilage, the matrix is interlaced with prominent collagen fiber bundles and the chondrocytes are more widely scattered than in hyaline cartilage. Elastic cartilage contains a network of elastic fibers which are histologically similar to elastin fibers. Hyaline cartilage is the most abundant cartilaginous tissue in humans and is present in primary cartilaginous joints where it unites two sections of bone. Most articular cartilage is hyaline cartilage. Secondary cartilaginous joints are formed by discs of fibrocartilage which join vertebrae in the vertebral column. As with other connective tissues, the formation of cartilaginous tissue is a complex biological process, involving the interaction of cells and fibers in a biochemical milieu.
A number of conditions are known in which the integrity of cartilage is compromised. Traumatic injury may occur by which the cartilage is disrupted, for example at articular surfaces. A number of degenerative diseases are also known in which general erosion of cartilaginous tissue occurs along with the appearance of fissures. Regeneration of damaged cartilage is a slow process.
A considerable amount of experimentation has been conducted in which the electrical environment of tissue has been altered in an attempt to stimulate tissue growth. These efforts originally concentrated on the use of electrode implants by which direct current was flowed across or into a bone non-union or abnormal union to stimulate repair of bone or articular cartilage. Due to numerous drawbacks, including the associated risks of surgery required to implant the electrodes, alternate, non-invasive techniques were pursued. While capacitively-generated electrostatic fields provided some beneficial results, the relatively large fields necessary were generally prohibitive. Finally, alternating, high-intensity electromagnetic fields were utilized to induce a voltage in bone. It was believed that by using the affected bone as a conductor, current flow through the bone could be induced which would produce therapeutic benefits.
Two typical prior art inductive devices are disclosed in U.S. Pat. No. 3,893,462 to Manning entitled, "Bioelectrochemical Regenerator and Stimulator Devices and Methods for Applying Electrical Energy to Cells and/or Tissue in a Living Body" and in U.S. Pat. No. 4,105,017 to Ryaby et al. entitled, "Modification of the Growth Repair and Maintenance Behavior of Living Tissue and Cells by a Specific and Selective Change in Electrical Environment." These investigators have focused on the use of large pulsed magnetic fields to produce moderately high induced currents in living tissue with well-defined "therapeutic" waveforms. In the area of regeneration of damaged cartilage, the work of Baker et al, which is disclosed in the article, "Electrical Stimulation of Articular Cartilage Regeneration," Annals New York Academy of Sciences, illustrates the direct electrical stimulation of tissue using an implanted bimetallic electrode to enhance regrowth of damaged articular cartilage. Therein, defects were created in the articular cartilage of the lateral femoral condyles of rabbits. The bimetallic electrodes were inserted into holes drilled through the condyle flares with a platinum wire from the electrode extending through the condyle at the defect and projecting slightly from the condyle surface. Both in vivo and in vitro experiments were carried out by Baker in this manner. A constant voltage was then applied for a period of from one to nine weeks. When compared with the control animals, the experimental animals demonstrated an increase in cellular proliferation and matrix production at the defect with regeneration of articular cartilage.
Pulsing electromagnetic fields have also been used experimentally to alter articular cartilage. In "Effects of Pulsing Electromagnetic Fields on Bone Growth and Articular Cartilage," Smith et al., Clin. Orthop. and Related Res., Vol. 181, exposure of immature rabbits to pulsing electromagnetic fields produced a significant increase in femoral articular cartilage glycosaminoglycan.
The inventors of the present invention have approached the problem of regulating cartilage growth from a different perspective. In its preferred embodiment, the present invention utilizes the interaction of fluctuating magnetic fields and preselected ions present in biological fluids to influence developmental processes. It should also be noted that although a possible role of magnetic fields beyond the galvanic action of induced currents is briefly mentioned in U.S. Pat. No. 3,890,953 to Kraus et al., to Applicants' knowledge no investigator has previously controlled cartilage growth in the manner set forth in the present invention.